title: Let-7g and miR-21 expression in non-small cell lung cancer: correlation with clinicopathological and molecular features.
abstract: MicroRNAs (miRNAs) play a key role in cancer pathogenesis and are involved in several human cancers, including non-small cell lung cancer (NSCLC). This study evaluated Let-7g and miR-21 expression by quantitative real-time PCR in 80 NSCLC patients and correlated the results with their main clinicopathological and molecular features. MiR-21 expression was significantly higher in NSCLC tissues compared to non-cancer lung tissues (p<0.0001), while no significant changes in Let-7g expression were observed between the tumor and normal lung tissues. Target prediction analysis led to the identification of 26 miR-21 and 24 Let-7g putative target genes that play important roles in cancer pathogenesis and progression. No significant association was observed between the analysed miRNAs and the main clinicopathological or molecular characteristics of the NSCLC patients, although both miRNAs were downregulated in squamous cell carcinomas compared to adenocarcinomas. Noteworthy, we observed a significant association between low Let-7g expression and metastatic lymph nodes at diagnosis (p=0.046), as well as between high miR-21 expression and K-Ras mutations (p=0.0003). Survival analysis did not show any significant correlation between prognosis and the analysed miRNAs, although the patients with a high Let-7g and miR-21 expression showed a significantly lower short-term progression-free survival (p=0.01 and p=0.0003, respectively) and overall survival (p=0.023 and p=0.0045, respectively). In conclusion, we showed that Let-7g and miR-21 expression was deregulated in NSCLC and we demonstrated a strong relationship between miR-21 overexpression and K-Ras mutations. Our data indicate that Let-7g and miR-21 profiling combined with the determination of K-Ras mutational status may be considered a useful biomarker for a more effective molecular characterization and clinical management of NSCLC patients.
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, I-56126 Pisa, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Capodanno
authors.forename: Laura
authors.initials: L
authors.lastname: Boldrini
authors.forename: Agnese
authors.initials: A
authors.lastname: Proietti
authors.forename: Greta
authors.initials: G
authors.lastname: Alì
authors.forename: Serena
authors.initials: S
authors.lastname: Pelliccioni
authors.forename: Cristina
authors.initials: C
authors.lastname: Niccoli
authors.forename: Armida
authors.initials: A
authors.lastname: D'Incecco
authors.forename: Federico
authors.initials: F
authors.lastname: Cappuzzo
authors.forename: Antonio
authors.initials: A
authors.lastname: Chella
authors.forename: Marco
authors.initials: M
authors.lastname: Lucchi
authors.forename: Alfredo
authors.initials: A
authors.lastname: Mussi
authors.forename: Gabriella
authors.initials: G
authors.lastname: Fontanini
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D011379:Prognosis
chemical_list: C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human